Pathology and genetics of thyroid carcinoma
Pathology and genetics of thyroid carcinoma
复制标题
DOI：
10.1002/jso.20700
复制
发表时间：
2006-12-15
影响因子：
2.5
通讯作者：
Delellis, Ronald A.
中科院分区：
文献类型：
--
作者：
Delellis, Ronald A.
甲状腺癌包括一组具有独特临床和病理特征的异质性肿瘤。在过去的15年中，分子技术在这些肿瘤研究中的应用已经阐明了与特定甲状腺肿瘤类型发展相关的关键遗传途径。在甲状腺乳头状癌（PTC）中，遗传事件涉及RET和TRK（重排）以及BRAF和RAS（突变），尽管RAS突变不常见，但PTC的滤泡变体除外。这些遗传改变在同一肿瘤中很少重叠，导致有丝分裂原活化蛋白激酶途径的信号异常。相比之下，滤泡癌中的遗传改变包括PAX 8-PPAR γ易位和RAS突变，而CTNNB 1和p53突变与低分化和未分化（间变性）甲状腺癌的发生和进展有关。RET的胚系突变是导致甲状腺髓样癌（MTC）遗传形式发展的原因，而该癌基因的体细胞突变在散发性MTC中发现的比例很大。这些研究的结果不仅为甲状腺肿瘤分类提供了额外的方法，而且还刺激了肿瘤诊断新方法和预后评估和潜在生物治疗策略的额外参数的发展。
Carcinomas of the thyroid comprise a heterogeneous group of neoplasms with distinctive clinical and pathological characteristics. Over the past 15 years, the application of molecular technologies to the study of these neoplasms has elucidated critical genetic pathways associated with the development of specific thyroid tumor types. In papillary thyroid carcinoma (PTC), genetic events involve RET and TRK (rearrangements) and BRAF and RAS (mutations), although RAS mutations are uncommon except in the follicular variant of PTC. These genetic alterations, which rarely overlap in the same tumor, result in signaling abnormalities in the mitogen-activated protein kinase pathway. In contrast, genetic alterations in follicular carcinomas include PAX8-PPAR gamma translocations and RAS mutations while mutations of CTNNB1 and p53 have been implicated in the development and progression of poorly differentiated and undifferentiated (anaplastic) thyroid carcinomas. Germline mutations of RET are responsible for the development of heritable forms of medullary thyroid carcinoma (MTC) while somatic mutations of this oncogene are found in a significant proportion of sporadic MTCs. The results of these studies not only have provided additional approaches to thyroid tumor classification, but also have stimulated the development of novel approaches to tumor diagnosis and additional parameters for prognostic assessment and potential biologic therapeutic strategies.